Aminolevulinic Acid-Based Tumor Detection and Therapy: Molecular Mechanisms and Strategies for Enhancement.


:Aminolevulinic acid (ALA) is the first metabolite in the heme biosynthesis pathway in humans. In addition to the end product heme, this pathway also produces other porphyrin metabolites. Protoporphyrin (PpIX) is one heme precursor porphyrin with good fluorescence and photosensitizing activity. Because tumors and other proliferating cells tend to exhibit a higher level of PpIX than normal cells after ALA incubation, ALA has been used as a prodrug to enable PpIX fluorescence detection and photodynamic therapy (PDT) of lesion tissues. Extensive studies have been carried out in the past twenty years to explore why some tumors exhibit elevated ALA-mediated PpIX and how to enhance PpIX levels to achieve better tumor detection and treatment. Here we would like to summarize previous research in order to stimulate future studies on these important topics. In this review, we focus on summarizing tumor-associated alterations in heme biosynthesis enzymes, mitochondrial functions and porphyrin transporters that contribute to ALA-PpIX increase in tumors. Mechanism-based therapeutic strategies for enhancing ALA-based modalities including iron chelators, differentiation agents and PpIX transporter inhibitors are also discussed.


Int J Mol Sci


Yang X,Palasuberniam P,Kraus D,Chen B




Has Abstract


2015-10-28 00:00:00












  • Role of Tricellular Tight Junction Protein Lipolysis-Stimulated Lipoprotein Receptor (LSR) in Cancer Cells.

    abstract::Maintaining a robust epithelial barrier requires the accumulation of tight junction proteins, LSR/angulin-1 and tricellulin, at the tricellular contacts. Alterations in the localization of these proteins temporarily cause epithelial barrier dysfunction, which is closely associated with not only physiological different...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Kohno T,Konno T,Kojima T

    更新日期:2019-07-20 00:00:00

  • Bevacizumab or PARP-Inhibitors Maintenance Therapy for Platinum-Sensitive Recurrent Ovarian Cancer: A Network Meta-Analysis.

    abstract:INTRODUCTION:Targeted agents such as bevacizumab (BEV) or poly (ADP-ribose) polymerase inhibitors (PARPi) which have been added as concomitant or maintenance therapies have been shown to improve progression-free survival (PFS) in patients with platinum-sensitive recurrent ovarian cancer (PS rOC). In the absence of dire...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Bartoletti M,Pelizzari G,Gerratana L,Bortot L,Lombardi D,Nicoloso M,Scalone S,Giorda G,Baldassarre G,Sorio R,Puglisi F

    更新日期:2020-05-27 00:00:00

  • Selective binding, self-assembly and nanopatterning of the Creutz-Taube ion on surfaces.

    abstract::The surface attachment properties of the Creutz-Taube ion, i.e., [(NH(3))(5)Ru(pyrazine)Ru(NH(3))(5)](5+), on both hydrophilic and hydrophobic types of surfaces were investigated using X-ray photoelectron spectroscopy (XPS). The results indicated that the Creutz-Taube ions only bound to hydrophilic surfaces, such as S...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Wang Y,Lieberman M,Hang Q,Bernstein G

    更新日期:2009-02-01 00:00:00

  • Copper-Free 'Click' Chemistry-Based Synthesis and Characterization of Carbonic Anhydrase-IX Anchored Albumin-Paclitaxel Nanoparticles for Targeting Tumor Hypoxia.

    abstract::Triple negative breast cancer (TNBC) is a difficult to treat disease due to the absence of the three unique receptors estrogen, progesterone and herceptin-2 (HER-2). To improve the current therapy and overcome the resistance of TNBC, there is unmet need to develop an effective targeted therapy. In this regard, one of ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Tatiparti K,Sau S,Gawde KA,Iyer AK

    更新日期:2018-03-13 00:00:00

  • Hypoxia-Mediated Decrease of Ovarian Cancer Cells Reaction to Treatment: Significance for Chemo- and Immunotherapies.

    abstract::Hypoxia, a common factor ruling the microenvironment composition, leads to tumor progression. In this hypoxic context, cytokines and cells cooperate to favor cancer development and metastasis. Tumor hypoxia is heterogeneously distributed. Oxygen gradients depend on the vicinity, functionality of blood vessels, and oxy...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Klemba A,Bodnar L,Was H,Brodaczewska KK,Wcislo G,Szczylik CA,Kieda C

    更新日期:2020-12-14 00:00:00

  • Signalling Overlaps between Nitrate and Auxin in Regulation of The Root System Architecture: Insights from the Arabidopsis thaliana.

    abstract::Nitrate (NO3-) and auxin are key regulators of root growth and development, modulating the signalling cascades in auxin-induced lateral root formation. Auxin biosynthesis, transport, and transduction are significantly altered by nitrate. A decrease in nitrate (NO3-) supply tends to promote auxin translocation from sho...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Asim M,Ullah Z,Oluwaseun A,Wang Q,Liu H

    更新日期:2020-04-20 00:00:00

  • Analysis of 2-(2-Phenylethyl)chromones by UPLC-ESI-QTOF-MS and Multivariate Statistical Methods in Wild and Cultivated Agarwood.

    abstract::Agarwood is the fragrant resinous material mainly formed from species of Aquilaria. 2-(2-phenylethyl)chromones, especially the highly oxidized 5,6,7,8-tetrahydro-2-(2-phenylethyl)chromones, are the main representative compounds from agarwood. It is important to determine whether agarwood in trade is from cultivated tr...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Li Y,Sheng N,Wang L,Li S,Chen J,Lai X

    更新日期:2016-05-23 00:00:00

  • Multiple Layers of CDK5R1 Regulation in Alzheimer's Disease Implicate Long Non-Coding RNAs.

    abstract::Cyclin-dependent kinase 5 regulatory subunit 1 (CDK5R1) gene encodes for p35, the main activator of Cyclin-dependent kinase 5 (CDK5). The active p35/CDK5 complex is involved in numerous aspects of brain development and function, and its deregulation is closely associated to Alzheimer's disease (AD) onset and progressi...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Spreafico M,Grillo B,Rusconi F,Battaglioli E,Venturin M

    更新日期:2018-07-11 00:00:00

  • Identification of RNA-Binding Proteins as Targetable Putative Oncogenes in Neuroblastoma.

    abstract::Neuroblastoma is a common childhood cancer with almost a third of those affected still dying, thus new therapeutic strategies need to be explored. Current experimental therapies focus mostly on inhibiting oncogenic transcription factor signalling. Although LIN28B, DICER and other RNA-binding proteins (RBPs) have repor...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Bell JL,Hagemann S,Holien JK,Liu T,Nagy Z,Schulte JH,Misiak D,Hüttelmaier S

    更新日期:2020-07-19 00:00:00

  • The Impact of IPTG Induction on Plasmid Stability and Heterologous Protein Expression by Escherichia coli Biofilms.

    abstract::This work assesses the effect of chemical induction with isopropyl β-D-1-thiogalactopyranoside (IPTG) on the expression of enhanced green fluorescent protein (eGFP) by planktonic and biofilm cells of Escherichia coli JM109(DE3) transformed with a plasmid containing a T7 promoter. It was shown that induction negatively...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Gomes L,Monteiro G,Mergulhão F

    更新日期:2020-01-16 00:00:00

  • Transcriptomic Analysis Reveals Candidate Genes Responsive to Sclerotinia scleroterum and Cloning of the Ss-Inducible Chitinase Genes in Morus laevigata.

    abstract::Sclerotinia sclerotiorum (Ss) is a devastating fungal pathogen that causes Sclerotinia stem rot in rapeseed (Brassica napus), and is also detrimental to mulberry and many other crops. A wild mulberry germplasm, Morus laevigata, showed high resistance to Ss, but the molecular basis for the resistance is largely unknown...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Jiang H,Jin X,Shi X,Xue Y,Jiang J,Yuan C,Du Y,Liu X,Xie R,Liu X,Li L,Wei L,Zhang C,Tong L,Chai Y

    更新日期:2020-11-07 00:00:00

  • Resolving the Ionotropic P2X4 Receptor Mystery Points Towards a New Therapeutic Target for Cardiovascular Diseases.

    abstract::Adenosine triphosphate (ATP) is a primordial versatile autacoid that changes its role from an intracellular energy saver to a signaling molecule once released to the extracellular milieu. Extracellular ATP and its adenosine metabolite are the main activators of the P2 and P1 purinoceptor families, respectively. Mounti...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Bragança B,Correia-de-Sá P

    更新日期:2020-07-15 00:00:00

  • Cypermethrin Induces Macrophages Death through Cell Cycle Arrest and Oxidative Stress-Mediated JNK/ERK Signaling Regulated Apoptosis.

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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Huang F,Liu Q,Xie S,Xu J,Huang B,Wu Y,Xia D

    更新日期:2016-06-17 00:00:00

  • Quercetin Potentiates Docosahexaenoic Acid to Suppress Lipopolysaccharide-induced Oxidative/Inflammatory Responses, Alter Lipid Peroxidation Products, and Enhance the Adaptive Stress Pathways in BV-2 Microglial Cells.

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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Sun GY,Li R,Yang B,Fritsche KL,Beversdorf DQ,Lubahn DB,Geng X,Lee JC,Greenlief CM

    更新日期:2019-02-21 00:00:00

  • Berberine Derivatives Suppress Cellular Proliferation and Tumorigenesis In Vitro in Human Non-Small-Cell Lung Cancer Cells.

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    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Chang JM,Kam KH,Chao WY,Zhao PW,Chen SH,Chung HC,Li YZ,Wu JY,Lee YR

    更新日期:2020-06-13 00:00:00

  • Clarifying the Ghrelin System's Ability to Regulate Feeding Behaviours Despite Enigmatic Spatial Separation of the GHSR and Its Endogenous Ligand.

    abstract::Ghrelin is a hormone predominantly produced in and secreted from the stomach. Ghrelin is involved in many physiological processes including feeding, the stress response, and in modulating learning, memory and motivational processes. Ghrelin does this by binding to its receptor, the growth hormone secretagogue receptor...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Edwards A,Abizaid A

    更新日期:2017-04-19 00:00:00

  • InDel Marker Based Estimation of Multi-Gene Allele Contribution and Genetic Variations for Grain Size and Weight in Rice (Oryza sativa L.).

    abstract::The market success of any rice cultivar is exceedingly dependent on its grain appearance, as well as its grain yield, which define its demand by consumers as well as growers. The present study was undertaken to explore the contribution of nine major genes, qPE9~1, GW2, SLG7, GW5, GS3, GS7, GW8, GS5, and GS2, in regula...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Gull S,Haider Z,Gu H,Raza Khan RA,Miao J,Wenchen T,Uddin S,Ahmad I,Liang G

    更新日期:2019-09-28 00:00:00

  • Endogenous Chemerin from PVAT Amplifies Electrical Field-Stimulated Arterial Contraction: Use of the Chemerin Knockout Rat.

    abstract::Background: We previously reported that the adipokine chemerin, when added exogenously to the isolated rat mesenteric artery, amplified electrical field-stimulated (EFS) contraction. The Chemerin1 antagonist CCX832 alone inhibited EFS-induced contraction in tissues with but not without perivascular adipose tissue (PVA...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Flood ED,Watts SW

    更新日期:2020-09-02 00:00:00

  • Role of Arginine Methylation in Alternative Polyadenylation of VEGFR-1 (Flt-1) pre-mRNA.

    abstract::Mature mRNA is generated by the 3' end cleavage and polyadenylation of its precursor pre-mRNA. Eukaryotic genes frequently have multiple polyadenylation sites, resulting in mRNA isoforms with different 3'-UTR lengths that often encode different C-terminal amino acid sequences. It is well-known that this form of post-t...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Ikeda T,Saito-Takatsuji H,Yoshitomi Y,Yonekura H

    更新日期:2020-09-04 00:00:00

  • Development of Molecular Markers for Detection of Acidovorax citrulli Strains Causing Bacterial Fruit Blotch Disease in Melon.

    abstract::Acidovorax citrulli (A. citrulli) strains cause bacterial fruit blotch (BFB) in cucurbit crops and affect melon significantly. Numerous strains of the bacterium have been isolated from melon hosts globally. Strains that are aggressively virulent towards melon and diagnostic markers for detecting such strains are yet t...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Islam MR,Hossain MR,Kim HT,Jesse DMI,Abuyusuf M,Jung HJ,Park JI,Nou IS

    更新日期:2019-06-02 00:00:00

  • Inheritance and Molecular Characterization of a Novel Mutated AHAS Gene Responsible for the Resistance of AHAS-Inhibiting Herbicides in Rapeseed (Brassica napus L.).

    abstract::The use of herbicides is an effective and economic way to control weeds, but their availability for rapeseed is limited due to the shortage of herbicide-resistant cultivars in China. The single-point mutation in the acetohydroxyacidsynthase (AHAS) gene can lead to AHAS-inhibiting herbicide resistance. In this study, t...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Huang Q,Lv J,Sun Y,Wang H,Guo Y,Qu G,Hu S

    更新日期:2020-02-17 00:00:00

  • Biofilm Formation and Immunomodulatory Activity of Proteus mirabilis Clinically Isolated Strains.

    abstract::Urinary tract infections (UTIs) and catheter-associated UTIs (CAUTIs) are the principal hospital-acquired infections. Proteus mirabilis is characterized by several virulence factors able to promote adhesion and biofilm formation and ameliorate the colonization of urinary tract and the formation of crystalline biofilms...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Fusco A,Coretti L,Savio V,Buommino E,Lembo F,Donnarumma G

    更新日期:2017-02-15 00:00:00

  • Micro Electromechanical Systems (MEMS) Based Microfluidic Devices for Biomedical Applications.

    abstract::Micro Electromechanical Systems (MEMS) based microfluidic devices have gained popularity in biomedicine field over the last few years. In this paper, a comprehensive overview of microfluidic devices such as micropumps and microneedles has been presented for biomedical applications. The aim of this paper is to present ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Ashraf MW,Tayyaba S,Afzulpurkar N

    更新日期:2011-01-01 00:00:00

  • Immunological mechanisms in the pathophysiology of non-alcoholic steatohepatitis.

    abstract::Non-alcoholic steatohepatitis (NASH) is characterized by the presence of steatosis, inflammation and hepatocyte injury and constitutes hepatic manifestation of the metabolic syndrome. The pathogenesis of NASH is complex and implicates cross-talk between different metabolically active sites, such as liver and adipose t...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Vonghia L,Michielsen P,Francque S

    更新日期:2013-10-01 00:00:00

  • CPP-Assisted Intracellular Drug Delivery, What Is Next?

    abstract::For the past 20 years, we have witnessed an unprecedented and, indeed, rather miraculous event of how cell-penetrating peptides (CPPs), the naturally originated penetrating enhancers, help overcome the membrane barrier that has hindered the access of bio-macromolecular compounds such as genes and proteins into cells, ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Ye J,Liu E,Yu Z,Pei X,Chen S,Zhang P,Shin MC,Gong J,He H,Yang VC

    更新日期:2016-11-14 00:00:00

  • The Role of miRNAs in Virus-Mediated Oncogenesis.

    abstract::To date, viruses are reported to be responsible for more than 15% of all tumors worldwide. The oncogenesis could be influenced directly by the activity of viral oncoproteins or by the chronic infection or inflammation. The group of human oncoviruses includes Epstein–Barr virus (EBV), human papillomavirus (HPV), ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Vojtechova Z,Tachezy R

    更新日期:2018-04-17 00:00:00

  • L-Arginine Inhibited Inflammatory Response and Oxidative Stress Induced by Lipopolysaccharide via Arginase-1 Signaling in IPEC-J2 Cells.

    abstract::This study aimed to explore the effect of L-arginine on lipopolysaccharide (LPS)-induced inflammatory response and oxidative stress in IPEC-2 cells. We found that the expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), cluster of differentiation 14 (CD14), nuclear factor-kap...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Qiu Y,Yang X,Wang L,Gao K,Jiang Z

    更新日期:2019-04-11 00:00:00

  • Endoglin Targeting: Lessons Learned and Questions That Remain.

    abstract::Approximately 30 years ago, endoglin was identified as a transforming growth factor (TGF)-β coreceptor with a crucial role in developmental biology and tumor angiogenesis. Its selectively high expression on tumor vessels and its correlation with poor survival in cancer patients led to the exploration of endoglin as a ...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Liu Y,Paauwe M,Nixon AB,Hawinkels LJAC

    更新日期:2020-12-25 00:00:00

  • Targeted Therapy in Melanoma and Mechanisms of Resistance.

    abstract::The common mutation BRAFV600 in primary melanomas activates the mitogen-activated protein kinase/extracellular-signal-regulated kinase (MAPK/ERK) pathway and the introduction of proto-oncogene B-Raf (BRAF) and mitogen-activated protein kinase kinase (MEK) inhibitors (BRAFi and MEKi) was a breakthrough in the treatment...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章,评审


    authors: Czarnecka AM,Bartnik E,Fiedorowicz M,Rutkowski P

    更新日期:2020-06-27 00:00:00

  • Stability Profiles and Therapeutic Effect of Cu/Zn Superoxide Dismutase Chemically Coupled to O-Quaternary Chitosan Derivatives against Dextran Sodium Sulfate-Induced Colitis.

    abstract::Superoxide dismutase (SOD) has attracted considerable attention on treatment of reactive oxygen species (ROS)-related disorders. We previously conjugated Cu/Zn SOD to O-quaternary chitosan derivatives (O-HTCC) to yield a polymer-enzyme conjugate O-HTCC-SOD that demonstrated superior therapeutic effect to native SOD. T...

    journal_title:International journal of molecular sciences

    pub_type: 杂志文章


    authors: Zhao N,Feng Z,Shao M,Cao J,Wang F,Liu C

    更新日期:2017-05-24 00:00:00